How long can women maintain their fertility?

News from September 15th, Beijing time, according to foreign media reports, with the help of modern medicine, today’s women can have children later than their ancestors. So, how long can women’s fertility extend? “This is the greatest inequality in nature,”Said Dagan Wells, professor of reproductive medicine at Oxford University in the UK. He was referring to the phenomenon of a gradual decline in female fertility from the age of 35, and this process is basically irreversible.

With age, the fertility of men also declines, but this decline often starts later-around the age of 40 to 45, the rate of occurrence is much slower than that of women. So, how to judge the exact time when a woman’s fertility starts to decline? How long does this decline process last before the natural fertility ability ends?

In thousands of years of history, many women began to conceive and give birth to children in their teens or early twenties—not unlike the Neanderthals who lived in Krapina, northern Croatia 30,000 years ago. Too big a difference. Local fossil remains indicate that these Neanderthals gave birth to their first children at the age of 15. Before the 1960s, women gave birth to their first child at about 21 years of age on average.

However, 2017 statistics show that the average childbearing age of women in all OECD countries is 30. In the same year, nearly half (44%) of live births in England and Wales had their mothers aged 30, while the average age at which Korean women gave birth to their first child was 31.

So, in the context of increasing reproductive age, how will women’s fertility be affected?

Quantity is important

Fertility treatment and the ability to freeze eggs allow more women to give birth later than in the past

Fertility treatment and the ability to freeze eggs allow more women to give birth later than in the past

For decades, scientists have believed that the decline in female fertility is related to the decrease in the number of eggs with age. If fertilized, these eggs have the potential to grow into babies.

Unlike men, male reproductive organs produce millions of fresh sperm every day, while women have immature eggs in their ovaries at birth, and the number of eggs will not increase after birth. As a woman ages, the number of eggs will steadily decline: from 1 million eggs at birth to 300,000 at adolescence; it drops to 25,000 at the age of 37; and only 1,000 at the age of 51. However, of all these eggs, only 300 to 400 eggs with fertility potential (usually 1 per month) will mature and eventually be released from the ovaries through the ovulation process. For reasons that are not yet fully understood, the remaining eggs will undergo a natural degradation process and will never be discharged.

Most girls start menstruating from the age of 9 to 13, but their ovaries will not start ovulating until at least one or two years later. A simple mathematical calculation can tell that a woman’s eggs usually run out after 33 years. The fertility of most women will end 8 years before menopause. For American women, this is about their 51st birthday.

Such a rough calculation does not take into account some natural differences among women, and can only roughly estimate how long a woman’s fertility can last. Sometimes, during the ovulation period of a certain month in a woman, the ovaries will release more than one egg, and sometimes there is no egg released for several months.

By measuring the level of anti-Mullerian hormone (AMH) in a woman’s blood, we can more accurately estimate the number of women’s eggs, the so-called “ovarian reserve.” We now know that for adult women with fertility, the anti-Müller tube hormone produced by their ovaries plays a vital role in the process of immature egg cells transforming into mature egg cells, creating all the energy for healthy babies. Biological prerequisites. A better-functioning ovary has a larger ovarian reserve and can produce more anti-Mullerian hormones. As women age and fertility declines, hormone levels also gradually decline: the average level of anti-Mullerian hormones in women aged 30 to 35 is about two-thirds of that of young women, while the level of women over 45 is 20 A quarter of multi-year-old women.

Embryologists have spent years studying the mechanism by which female fertility declines with age and hope to find a way to slow this trend. Studies have found that ovarian reserve is regulated by genes, but women’s life experiences, such as stress, exposure to radiation or toxic chemicals, and even experiences in the womb, all determine the number of eggs in the future.

Quality problem

However, a woman’s fertility does not only depend on the number of eggs. Quality is also important, and evaluating the quality of eggs is more technically challenging than estimating the number of eggs. While the number of eggs decreases as women age, the quality of the chromosomes and DNA inside each egg will gradually decline.

Chromosomal abnormalities in human eggs are very common, and this should not be considered a particularly abnormal condition. In most cases, this occurs in the eggs of all women, even young women, but it should be noted that this chromosomal abnormality will increase with age.

For women in their 20s, a quarter of their eggs may have chromosomal abnormalities. Among women between 30 and 35 years old, this proportion will rise to 40%, and it has “increased exponentially since then.” . Over the age of 35, the frequency of chromosomal abnormalities in these eggs increases by about 0.5% per month, so for women in their early 40s, up to three-quarters of the eggs will have chromosomal abnormalities.

The chromosomal abnormality of the egg cell does not necessarily mean that a woman is infertile, but it does mean that the egg cell will have a lower chance of survival during her menstrual cycle.

We can think of chromosomes as a bunch of tightly wound deoxyribonucleic acid (DNA), which preserves the genetic information needed for the development of organisms. A human egg contains 23 chromosomes-half of the body’s genetic code comes from the mother-it needs to combine with 23 chromosomes from sperm to develop into a viable embryo. If the egg has too many or too few chromosomes, or is broken or damaged, it often fails to develop normally. In some cases, babies may still have chromosomal abnormalities at birth, such as Down syndrome.

For very early embryos, most chromosomal abnormalities are often fatal, which may prevent the embryo from implanting into the endometrium or cause a very early miscarriage, which usually occurs between 5 to 8 weeks of pregnancy.

It is well known that older women have a higher risk of chromosomal abnormalities in their eggs, but a recent European study found that young women from 13 to early 20s also have high levels of chromosomal abnormalities. The results of the study show that women’s fertility time follows the “n”-shaped pattern, and the peak of fertility occurs at around 25 years of age. Both younger and older women have lower fertility levels.

Inside the egg, defective mitochondria—the tiny organelles that provide energy to the cell, all inherited from the mother—may also become a problem for older women. Studies have shown that as many as half of the mitochondrial DNA of women over the age of 35 have mutations in their eggs, compared with one-third of young women.

An egg needs about 40,000 copies of mitochondrial DNA to make an embryo. By the age of 35, this decline speeds up. Most women are basically infertile by the age of 45. Importantly, this is before menopause. A few years, even ten years. Everyone knows that with age, fertility will decline, but the degree of this decline still surprises many people.

It is wrong to focus solely on female fertility. Some studies have shown that the quality of men’s sperm starts in their 20s and will decline with age. Studies have found that when older men’s sperm carry more DNA mutations, the sperm’s swimming ability decreases by 0.7% every year. Compared to mothers, older fathers also pass on more mutations to their children.

Best egg

The human egg is an extraordinary cell. It is the largest cell in the human body and has unique characteristics. The ability of oocytes to cease activity during growth and remain dormant for several years, even decades, until finally ovulation. Studies have shown that the ability of oocytes to keep their chromosomes stable during dormancy determines their ability to develop into embryos and babies.

The study also found that the human egg has undergone at least 9 months of growth and maturation in the ovary, and then the released egg is released during the ovulation period. The quality of the released egg is all the health and environmental factors that have been affected in the past 9 months. The vertex of influence. During this period, psychological stress, radiation, or toxic chemicals, etc., will adversely affect the developing eggs.

Perhaps interestingly, the duration of this “incubation period”-from the recovery of the oocyte from dormancy to the beginning of development-is surprisingly similar to the number of months a baby spends in the womb before birth. At this stage of gradual maturity, the egg will develop the resources needed for fertilization.

The egg must have a very rich resource. In the first three days after fertilization, the embryo cannot really make anything for itself—it does not transcribe its own genes, nor does it make proteins—but it depends entirely on what the egg provides to it. . A mature egg is more likely to have better resources than an immature egg.

Although science can hardly change the number of eggs determined by nature (or heredity) in a woman’s life, there are some methods we can take to improve or save the quality of eggs. For example, adopting a healthier lifestyle, exercising regularly, reducing stress, and ensuring that health problems such as hypothyroidism and other autoimmune diseases are well controlled can all help.

Researchers found that after administering antioxidant coenzyme Q10 to female mice, very good results were obtained. The mice taking this supplement produced better quality eggs, more rational chromosomal arrangement, and better mitochondrial function. Compared with mice that did not take supplements, they were more likely to give birth to live pups. However, this result has not been replicated in humans.

New technology is not the end

Various factors that prevent an egg from fertilizing and developing into a fetus make childbirth seem incredible

Various factors that prevent an egg from fertilizing and developing into a fetus make childbirth seem incredible

With age, mothers not only need to deal with the decline in fertility, but also need to deal with greater risks during pregnancy and childbirth. In the “The First and Second Trimester Evaluation of Risk” (Faster) trial funded by the National Institute of Child Health and Human Development (NICHD), the researchers analyzed more than 36,000 women’s Health records. The results found that mothers over the age of 40 are two to three times more likely to develop health problems such as diabetes and high blood pressure during pregnancy than young women; they are more likely to experience placental bleeding, caesarean section, and loss of children during the second trimester. Twice.

For first-time mothers aged 40 and over, their children will also have an increased risk of health problems at birth, such as low birth weight and congenital abnormalities. The risk of their babies being born prematurely increased by 50%, so the risk of needing neonatal intensive care after birth also increased.

However, this is still only half the truth. Older fathers also bring additional health risks to their children. Babies with older fathers are more likely to be born prematurely or have a lower birth weight and have a higher risk of seizures. Some studies have also found that the increase in the age of the father is associated with an increased risk of diseases such as autism and ADHD, but the evidence is not clear enough.

Is it possible for women’s fertility to be extended? How long can it be extended? In many cases, when nature creates inequality, science tries to eliminate it. In September 2019, Erramatti Mangamma, 74 years old in southern India, became the oldest new mother in the world. After 57 years of infertility, she became pregnant with twin girls through in vitro fertilization (IVF). Three years ago, Daljinder Kaur, 72, in northern India, gave birth to a son after nearly 50 years of marriage and two failed IVF.

Scientists are developing new techniques to ensure that the best eggs are used for IVF

Scientists are developing new techniques to ensure that the best eggs are used for IVF

In the past few decades, major advances in reproductive medicine have greatly improved the safety, success rate, availability and affordability of artificial reproductive technology. In 2014, approximately 230 women aged 50 and over in the UK gave birth to babies each year, while in the US, 9% of women who gave birth for the first time were over 35 years old.

However, as we have seen, these techniques are still limited to a certain extent by the age of the egg. This is not only because of the effect of aging on the DNA of eggs, but also because older eggs are exposed to environmental toxins for longer periods of time. Of course, in vitro fertilization using eggs donated by young women is also possible. Now, almost all fertility clinics in the world provide women with the option of storing eggs, allowing them to freeze the eggs in time until they are thawed, fertilized and transplanted into the uterus when they are ready.

The difficulties that older women experience when they want to give birth have nothing to do with the uterus, but with the egg. The chromosomal abnormality is the core problem. The egg is the seed, not the soil. Many early stages of human development are determined by the material provided by the egg.

With the help of techniques such as pre-implantation genetic testing of embryos, embryologists are studying how to identify the best eggs that can be used for IVF treatment. Other technologies such as mitochondrial replacement therapy are also helping mothers with defective eggs give birth to healthy children. However, although these scientific measures can help extend the time for women to maintain fertility, there is no doubt that fertility cannot be maintained indefinitely. The decline in women’s natural fertility is both inevitable and common. (Ren Tian)